PROJECT SUMMARY/ABSTRACT Oregon Health & Science University and the Fred Hutchinson Cancer Research Center have worked over the past decade to develop ex vivo drug profiling to guide a rationale decision-making in assigning drugs to cancer patients, thereby improving patient outcomes and reducing healthcare costs. A number of recent breakthroughs, many developed through our partnership, have dramatically improved on nearly all aspects of ex vivo drug testing. Our work to date has led to numerous compassionate-use cases as well as new investigator initiated clinical trials. Recognizing the broad utility for a clinic-friendly ex vivo drug sensitivity platform, we set up a commercial entity, SEngine Precision Medicine, whose mission is to provide functional testing of patient derived tumor cells for research, clinical studies, and drug development. Here we seek to move beyond proof of concept in the assay toward wider adoption by cancer research centers, community hospitals, and individual users. We will benchmark the assay?s predictive performance in both ?N of 1? settings and in prospective observational studies, and use this baseline performance to drive the development of methods to further improve its predictive value. We will continue to optimize drug selection by integrating ex vivo drug testing with patient specific genomic profiling and clinical data. In parallel, we will develop a reporting system, based upon requirements analysis, for potential end users such as clinicians and academic research centers. OHSU will provide expertise in precision medicine for AML, functional testing of primary leukemia cells, and clinical trials and will assist with assay optimization. FHCRC will provide expertise in functional testing of cells derived from solid tumors, focusing first on breast cancer, cancer genomics, and clinical trials; and will assist with assay optimization and benchmarking. SEngine will develop CLIA certified assays, optimize sample analysis workflows, and develop a reporting system for end users. All three sites will work together to demonstrate inter-institutional proficiency of the assays. At least five additional academic centers have agreed to provide patient derived tumor cells for this project and we anticipate this number will increase during the granting period. The partnering institutions will also provide essential feedback for our performance and reporting system. Our end goals for this project are to produce a refined functional genomic platform based on ex vivo drug screens, a user-friendly reporting interface, and adoption of the technology in the clinical care decision-making process.